Experimental Cholesterol-Busting Drug Shows Promise: Study

For 45-year-old Monty Reid, dealing with the consequences of uncontrollable high cholesterol has been a way of life.

He has seen family members die in their 20s from heart attacks. Now he, too, has been told he has coronary artery disease.

"I have been on every type of cholesterol medication since I was 9 years old," said Reid, who was diagnosed with an inherited form of high cholesterol as a child. These days he takes maximum doses of two cholesterol-lowering medications -- rosuvastatin and ezetimibe -- yet he still can't get his cholesterol under control.

Today, along with lifestyle changes, a class of medications called statins is first-line therapy for lowering cholesterol. These drugs have been shown to lower levels of bad cholesterol and cut the risk of death for those who take them. But they do not work for all patients. Up to 10 percent of patients experience significant side effects, including muscle pain. An even greater number are unable to get their LDL-C, or "bad cholesterol," down to a range that has been shown to decrease heart disease.

Now, new research suggests that doctors treating patients like Reid may one day have another weapon in the arsenal against high cholesterol. In a study published in the New England Journal of Medicine, researchers looked at a new, experimental class of cholesterol-busting medication -- known for now at least as PCSK9 inhibitors.

In the study, supported by the pharmaceutical companies Regeneron and Sanofi, researchers led by Dr. Evan Stein of the Metabolic and Atherosclerosis Research Center in Cincinnati, found the drug, called REGN727, could decrease bad cholesterol by as much as 65 percent in healthy individuals. More surprisingly, in participants who were already taking the powerful cholesterol-lowering medication atorvastatin -- better known by the trade name Lipitor -- adding this drug further decreased their bad cholesterol by as much as 61 percent. During this preliminary study, there were no side effects that were serious enough to halt the research -- another positive sign.

Stein further noted that the experimental drug may lead to "even greater reductions in LDL-C than the most effective statins."

Dr. Robert Eckel, former president of the American Heart Association, said that if the drug indeed lives up to its promises, it could potentially benefit many patients he sees every day. "Despite the proven benefit of statins in reducing [cardiovascular] risk, additional LDL-C lowering therapies are needed for patients with several genetic disorders that cause high levels of LDL-C and those with statin intolerance." These patients, he added, make up 40 percent of the patients treated at his clinic.

Dr. Dan Rader, a professor of medicine at the University of Pennsylvania who also acts as a consultant for Regeneron and Sanofi, said a new offering for these patients would be a welcome development. "It is worth stating that we really don't have great options for add-on therapy to statins or for statin-intolerant patients.

"Inhibitors of PCSK9 are perhaps the most exciting new approach to LDL-lowering based on very strong human genetics supporting the efficacy and safety of this approach."

And Dr. Christopher Cannon, a professor of medicine at Brigham and Women's Hospital in Boston, called PCSK9 inhibitors a "very important new class of drug. It reduces a major risk factor [for heart disease] by nearly two-thirds."

But some doctors warned that, although promising, the results of this study are just one step in a long process before these drugs can reach the market.

"It is an early study," said Dr. Harlan Krumholz, a professor of medicine at Yale University, said. "It is information that can be used to mount a rationale for further study and investment. But for patients, it is far too early to tell."

Dr. Scott Grundy, at the University of Texas Southwestern Medical Center at Dallas, echoed the sentiment. "PCSK9 inhibitors hold a lot of promise, but there is a long road between their ability to lower LDL and proof that they are practical and reduce risk for [coronary heart disease]."

Still, Reid, who was enrolled in the study and later found out he received REGN727, said he was shocked at the results.

"I've never seen my cholesterol this low," he said. "Seeing my [bad cholesterol levels] in the 60s was remarkable."

Now that the study is over, whether this drug will ever be available to Reid again remains to be seen. But he said he believes it could make a big difference for him and others like him.

"It will take a burden off of me," he said. "It is hard to be in your 30s, and someone tells you have heart disease."